Structure, mapping and expression of the human gene encoding the homeodomain protein, SIX2

Boucher, Catherine; Winchester, Catherine; Hamilton, Graham; Winter, Alan D.; Johnson, Keith; Bailey, Mark E.S.

doi:10.1016/s0378-1119(00)00105-0

Cited by 30 publications

(27 citation statements)

References 22 publications

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“…Furthermore, genetic linkage has been shown between sine oculis and D-SIX3, between SIX2 and SIX3, and among SIX1, SIX4 and SIX6 (Boucher et al 2000). Based on these observations, it has been proposed that a single ancestral cluster of three genes was present in the ancestor of vertebrates and Drosophila, and that the two clusters in vertebrates originated from a single cluster through a genome-wide duplication event (Boucher et al 2000). The present survey uncovered single candidate genes for each of the three subclasses.…”

Section: Six Classmentioning

confidence: 97%

“…One is composed of sine oculis, SIX1 and SIX2 (SIX1/2 subclass), the second one of Drosophila D-SIX3 and vertebrate SIX3 and SIX6 (SIX3/6 subclass), and the third one of Drosophila D-SIX4 and vertebrate SIX4 and SIX5 (SIX4/5 subclass). Furthermore, genetic linkage has been shown between sine oculis and D-SIX3, between SIX2 and SIX3, and among SIX1, SIX4 and SIX6 (Boucher et al 2000). Based on these observations, it has been proposed that a single ancestral cluster of three genes was present in the ancestor of vertebrates and Drosophila, and that the two clusters in vertebrates originated from a single cluster through a genome-wide duplication event (Boucher et al 2000).…”

Section: Six Classmentioning

confidence: 99%

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A genomewide survey of developmentally relevant genes in Ciona intestinalis

et al. 2003

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Homeobox-containing genes play crucial roles in various developmental processes, including body-plan specification, pattern formation and cell-type specification. The present study searched the draft genome sequence and cDNA/EST database of the basal chordate Ciona intestinalis to identify 83 homeobox-containing genes in this animal. This number of homeobox genes in the Ciona genome is smaller than that in the Caenorhabditis elegans, Drosophila melanogaster, human and mouse genomes. Of the 83 genes, 76 have possible human orthologues and 7 may be unique to Ciona. The ascidian homeobox genes were classified into 11 classes, including Hox class, NK class, Paired class, POU class, LIM class, TALE class, SIX class, Prox class, Cut class, ZFH class and HNF1 class, according to the classification scheme devised for known homeobox genes. As to the Hox cluster, the Ciona genome contains single copies of each of the paralogous groups, suggesting that there is a single Hox cluster, if any, but genes orthologous to Hox7, 8, 9 and 11 were not found in the genome. In addition, loss of genes had occurred independently in the Ciona lineage and was noticed in Gbx of the EHGbox subclass, Sax, NK3, Vax and vent of the NK class, Cart, Og9, Anf and Mix of the Paired class, POU-I, III, V and VI of the POU class, Lhx6/7 of the LIM class, TGIF of the TALE class, Cux and SATB of the Cut class, and ZFH1 of the ZFH class, which might have reduced the number of Ciona homeobox genes. Interestingly, one of the newly identified Ciona intestinalis genes and its vertebrate counterparts constitute a novel subclass of HNF1 class homeobox genes. Furthermore, evidence for the gene structures and expression of 54 of the 83 homeobox genes was provided by analysis of ESTs, suggesting that cDNAs for these 54 genes are available. The present data thus reveal the repertoire of homeodomain-containing transcription factors in the Ciona genome, which will be useful for future research on the development and evolution of chordates.

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Section: Six Classmentioning

confidence: 97%

Section: Six Classmentioning

confidence: 99%

A genomewide survey of developmentally relevant genes in Ciona intestinalis

et al. 2003

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“…After being washed with water, fixed samples were dehydrated by sequentially increasing concentrations of ethanol, cleared in xylene, and then embedded in paraffin. The embedded samples were sectioned at a 5-m thickness, and each section was transferred onto a slide, dewaxed in xylene, rehydrated by sequentially decreasing concentrations of ethanol, stained in hematoxylin solution [0.1% hematoxylin, 5% K 2 Al 2 (SO 4 ) 4 , 0.02% NaIO 3 , 5% chloral hydrate, 0.1% citric acid, and 20% glycerol] for 15 min, and differentiated in water. Then, the sections were counterstained in eosin solution (0.25% eosin Y, 0.55% acetic acid, and 60% ethanol) for 30 min; differentiated sequentially in 70, 80, and 90% ethanol solutions; dehydrated in absolute ethanol; cleared in xylene; and coverslipped.…”

Section: Construction Of Six4 Gene Targeting Vectormentioning

confidence: 99%

Six4, a Putative myogeninGene Regulator, Is Not Essential for Mouse Embryonal Development

Ozaki¹,

Watanabe²,

Takahashi³

et al. 2001

Molecular and Cellular Biology

125

100

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Six4 is a member of the Six family genes, homologues of Drosophila melanogaster sine oculis. The gene is thought to be involved in neurogenesis, myogenesis, and development of other organs, based on its specific expression in certain neuronal cells of the developing embryo and in adult skeletal muscles. To elucidate the biological roles of Six4, we generated Six4-deficient mice by replacing the Six homologous region and homeobox by the ␤-galactosidase gene. 5-Bromo-4-chloro-3-indolyl-␤-D-galactopyranoside staining of the heterozygous mutant embryos revealed expression of Six4 in cranial and dorsal root ganglia, somites, otic and nasal placodes, branchial arches, Rathke's pouch, apical ectodermal ridges of limb buds, and mesonephros. The expression pattern was similar to that of Six1 except at the early stage of embryonic day 8.5. Six4-deficient mice were born according to the Mendelian rule with normal gross appearance and were fertile. No hearing defects were detected. Six4-deficient embryos showed no morphological abnormalities, and the expression patterns of several molecular markers, e.g., myogenin and NeuroD3 (neurogenin1), were normal. Our results indicate that Six4 is not essential for mouse embryogenesis and suggest that other members of the Six family seem to compensate for the loss of Six4.

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“…Another lineage analysis revealed that a homeodomain transcriptional regulator, Six2, is required to maintain a nephron progenitor population, ensuring the development of a full complement constituting nephrons. However, Six2 is also expressed in other fetal organs, such as the skeletal muscle, limbs, heart, eyes, and middle ears [2,8]. Osr1 and Six2 interact synergistically to maintain nephron progenitor cells during kidney organogenesis [9].…”

Section: Introductionmentioning

confidence: 99%

Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in Mice

Toyohara

Mae

Sueta

et al. 2015

Stem Cells Translational Medicine

137

138

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Acute kidney injury (AKI) is defined as a rapid loss of renal function resulting from various etiologies, with a mortality rate exceeding 60% among intensive care patients. Because conventional treatments have failed to alleviate this condition, the development of regenerative therapies using human induced pluripotent stem cells (hiPSCs) presents a promising new therapeutic option for AKI. We describe our methodology for generating renal progenitors from hiPSCs that show potential in ameliorating AKI. We established a multistep differentiation protocol for inducing hiPSCs into OSR1 + SIX2 + renal progenitors capable of reconstituting three-dimensional proximal renal tubule-like structures in vitro and in vivo. Moreover, we found that renal subcapsular transplantation of hiPSC-derived renal progenitors ameliorated the AKI in mice induced by ischemia/reperfusion injury, significantly suppressing the elevation of blood urea nitrogen and serum creatinine levels and attenuating histopathological changes, such as tubular necrosis, tubule dilatation with casts, and interstitial fibrosis. To our knowledge, few reports demonstrating the therapeutic efficacy of cell therapy with renal lineage cells generated from hiPSCs have been published. Our results suggest that regenerative medicine strategies for kidney diseases could be developed using hiPSC-derived renal cells. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:980-992 SIGNIFICANCEThis report is the first to demonstrate that the transplantation of renal progenitor cells differentiated from human induced pluripotent stem (iPS) cells has therapeutic effectiveness in mouse models of acute kidney injury induced by ischemia/reperfusion injury. In addition, this report clearly demonstrates that the therapeutic benefits come from trophic effects by the renal progenitor cells, and it identifies the renoprotective factors secreted by the progenitors. The results of this study indicate the feasibility of developing regenerative medicine strategy using iPS cells against renal diseases.

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Structure, mapping and expression of the human gene encoding the homeodomain protein, SIX2

Cited by 30 publications

References 22 publications

A genomewide survey of developmentally relevant genes in Ciona intestinalis

A genomewide survey of developmentally relevant genes in Ciona intestinalis

Six4, a Putative myogeninGene Regulator, Is Not Essential for Mouse Embryonal Development

Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in Mice

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